This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The study utilizes both SIV-infected and colony born SIV negative sooty mangabeys housed at Yerkes to investigate the role of cellular immune responses in maintaining nonpathogenic SIV infection in a number of different ways. It has been previously shown that naturally SIV-infected sooty mangabeys were able to mount a substantial Th1-type SIV-specific cellular immune response comparable in magnitude to SIV-infected rhesus macaques. Subsequently, the early host response to SIV in primary infection was compared in SIV-infected rhesus macaques and sooty mangabeys. While a robust SIV-specific cellular immune response was mounted in both species, rhesus macaques displayer greater and longer non-virus-specific immune activation in acute infection. Moreover, CD4+ T lymphocyte apoptosis and increased TNF-related apoptosis inducing ligand were seen only in macaques. This data points to the presence of species-specific differences in the early innate immune response;it appears that this could contribute to differential immune activation in natural and non-natural hosts of SIV infection.